Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design: sustained DORIS or LLDAS for at least 6 months is sufficient while their attainment for at least 24 months ensures high specificity for damage-free progression.

OBJECTIVES: Treatment targets in systemic lupus erythematosus (SLE) have been validated in unselected-in terms of severity-cohorts, which limits their generalisability. We assessed remission (Definition of Remission in SLE (DORIS)) and Lupus Low Disease Activity State (LLDAS) in a historical cohort of 348 patients with active moderate-to-severe disease and median follow-up of 5 years. METHODS: Active SLE was defined as Physician Global Assessment ≥1.5 and/or SLE Disease Activity Index 2000 ≥6, requiring therapy intensification. DORIS/LLDAS, organ damage, flares and adverse events were monitored. Shared frailty survival, generalised linear models and K-means clustering were applied. RESULTS: Sustained DORIS and LLDAS for ≥6 months occurred in 41.1% and 80.4%, respectively, and resulted in reduced damage accrual (HR: 0.58; 95% CI 0.36 to 0.93 and 0.61; 0.43 to 0.86) and severe flares (HR: 0.14; 0.08 to 0.27 and 0.19; 0.13 to 0.27). LLDAS without DORIS was also protective (HR: 0.65; 0.43 to 0.98 for damage, 0.49; 0.36 to 0.67 for flares). Models fitting increasing duration of targets showed that DORIS ≥50% and LLDAS ≥60% of time, or alternatively, ≥24 and ≥36 months, achieved optimal balance between feasibility (20.2-41.7%) and specificity (73.3-86.1%) for damage-free outcome. These targets were linked to reduced serious adverse events (risk ratio (RR): 0.56-0.71), hospitalisation (RR: 0.70) and mortality (RR: 0.06-0.13). Patients with predominant arthritis and mucocutaneous disease experienced reduced DORIS/LLDAS, compared with counterparts with major organ involvement. Conventional drugs were more frequently used in the former group, whereas potent immunosuppressive/biological agents in the latter. CONCLUSIONS: In moderate-to-severe SLE, sustained DORIS/LLDAS for at least 6 months is sufficient, while attainment for at least 24 months ensures higher specificity for damage-free progression, thus facilitating treat-to-target strategies and clinical trials. Arthritis and skin disease represent unmet therapeutic needs that could benefit from novel biologics.

Optimizing Patient Care: A Systematic Review of Multidisciplinary Approaches for SLE Management.

Systemic lupus erythematosus (SLE) is characterized by multisystemic clinical manifestations ranging from a relatively mild involvement to potentially life-threatening complications. Due to this complexity, a multidisciplinary (MD) approach is the best strategy for optimizing patients' care. The main aim of this systematic literature review (SLR) was to scrutinize the published data regarding the MD approach for the management of SLE patients. The secondary objective was to evaluate the outcomes of the MD approach in SLE patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. We performed an SLR to retrieve articles available in English or Italian listed in PubMed, Embase, Cinahl, and Cochrane Library concerning the MD approach used in observational studies and clinical trials. Four independent reviewers performed the study selection and data collection. Of 5451 abstracts evaluated, 19 studies were included in the SLR. The MD approach was most frequently described in the context of SLE pregnancy, reported in 10 papers. MD teams were composed of a rheumatologist, except for one cohort study; a gynecologist; a psychologist; a nurse; and other health professionals. MD approaches had a positive impact on pregnancy-related complications and disease flares and improved SLE psychological impact. Although international recommendations advise an MD approach for managing SLE, our review highlighted the paucity of data supporting this strategy, with most of the available evidence on the management of SLE during pregnancy.

Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC).

Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.

Microstructures formation in a seemingly ideal homogeneous mixture of ethanol and methanol: An experimental evidence and two-dimensional correlation spectroscopy approach.

An anomalous solution behavior at the molecular scale was observed for macroscopically homogeneous mixtures of methanol and ethanol. Two-dimensional Raman correlation spectroscopy was used to elucidate the possible existence of microstructures formed in the mixture. The result suggests that separate methanol and ethanol clusters are formed without heterohydrogen bonding between different alcohol species. Supramolecular structures seem to be formed by the interaction of such clusters with each other through cohesion and dispersion forces, but not through direct hydrogen bonding connections.

Fast determination of thyroid stimulating hormone in human blood serum without chemical preprocessing by using infrared spectroscopy and least squares support vector machines.

The least squares support vector machines (LS-SVM) was used to model infrared spectral data for TSH hormone secreted by thyroid, which regulates the basal metabolic rate. This model was used for direct estimation of the content of TSH in blood serum samples, and the results were comparable with those obtained with the conventional analytical method based on chemoluminescence methodology. Excellent agreement was observed between the conventional method and the newly developed calibration model based in analysis of spectral data with LS-SVM. The latter has clear advantages, because it is fast and requires no reagent once the measurements were done directly in the serum by using a simple mid-infrared spectrometer in the ATR mode. An important advantage observed in this calibration method based on LS-SVM is the remarkable capacity to avoid overfitting in the model-building step, that is, the developed method is highly robust.

Estudo comparativo dos resultados de testes de resolução temporal em jovens adultos / Comparative study of temporal resolution test results in young adults

RESUMO Objetivo: comparar o desempenho de universitários nos testes de resolução temporal, Gaps In Noise e Randon Gap Detection Test. Métodos: a população avaliada foi composta por 51 adultos, de ambos os sexos, na faixa etária de 18 a 35 anos, com ausência de histórico otológico e/ou audiológico, sem alterações neurológicas e transtornos de aprendizagem. Os procedimentos utilizados na pesquisa foram os testes Randon Gap Detection Test e Gaps In Noise, realizado a 40 dBNS. Resultados: os resultados demonstraram diferença estatisticamente significante na comparação entre o tempo de percepção dos intervalos de silêncio nos testes Randon Gap Detection Test e Gaps In Noise, para ambos os sexos. Não houve diferença estatisticamente significante com relação à orelha em que o teste Gaps In Noise foi iniciado. Os limiares de detecção do gap de silêncio no teste Gaps In Noise foram menores em milissegundos com relação aos limiares obtidos no Randon Gap Detection Test. Conclusão: há influência do sexo nos resultados do teste Randon Gap Detection Test, com melhor desempenho do sexo masculino. Para o teste Gaps In Noise, os critérios de sexo e orelha em que o teste foi iniciado, não influenciaram os resultados. A comparação entre os testes Randon Gap Detection Test e Gaps In Noise, para ambos os sexos, demonstrou melhor desempenho para o teste Gaps In Noise, com a percepção do gap em intervalos de tempo menores.

ABSTRACT Purpose: to compare the performance of adults on tests of temporal resolution, and Gaps In Noise Random Gap Detection Test. Methods: the population studied consisted of 51 students of both genders, aged 18 to 35, with no otologic and/or audiological history, without neurological and learning disorders. The procedures used in the research were Random Gap Detection Test and Gaps In Noise tests, performed at 40 dBSL. Results: the results showed statistically significant difference when comparing the perception of time intervals of silence Random Gap Detection Test and Gaps In Noise tests for both genders. There was no statistically significant difference regarding the ear in which the Gaps In Noise test was initiated. The detection threshold of the gap of silence at the Gaps In Noise test was lower in miliseconds in relation to thresholds obtained in Random Gap Detection Test. Conclusion: there is influence of gender on test results Random Gap Detection Test and Gaps In Noise, with best male performance. The ear and gender criteria did not influence the outcome of the Gaps In Noise gap detection test. The comparison between of both tests (Random Gap Detection Test and Gaps In Noise) demonstrated a better performance in Gaps In Noise test, with the perception of gap in smaller time intervals.

Mismatch Negativity (MMN) response studies in elderly subjects.

UNLABELLED: Mismatch Negativity is an endogenous potential which reflects the processing of differences incurred in the acoustic stimulus. AIM: to characterize MMN responses in elderly subjects and compare with adult subjects. MATERIALS AND METHODS: prospective study involving 30 subjects, 15 men and 15 women, aged between 60 and 80 years and 11 months. Statistical test: Mann-Whitney. The subjects went through medical evaluation, threshold tonal audiometry, immittance tests, otoacoustic emissions and short and long latency auditory potentials (MMN). RESULTS: mean latency was 161.33 ms (CZA2) and 148.67 ms (CZA1), in women; of 171 ms (CZA2) and 159.07 ms (CZA1), men. Mean amplitude was -2.753 microV (CZA2) and -2.177 microV (CZA1), women; -1.847 microV (CZA2) and -1.953 microV (CZA1), men. As to the right and left hemispheres, mean latency variable of 166 ms (CZA2) and 153.87 ms (CZA1); for the amplitude variable, mean value of -2.316 microV (CZA2) and -2.065 microV (CZA1). CONCLUSION: there is no statistically significant difference between the latency and amplitude when we compared males and females, right and left sides in the elderly and between chronologic ages between adults and elderly subjects.

Relação entre ausência do reflexo do músculo estapédio e presença de distúrbios do processamento auditivo (central) / The relationship between the lack of stapedial muscle reflex and the presence of (central) auditory processing disorders

Objetivo caracterizar e relacionar os achados do reflexo acústico do músculo estapédio em indivíduos com diagnóstico de distúrbios do processamento auditivo (central). Métodos pesquisa transversal descritiva retrospectiva, submetida e aprovada pelo Comitê de Ética em Pesquisa, sob o protocolo nº 0047/11. Amostra constituiu-se de 83 prontuários de indivíduos de ambos os gêneros (57 masculino e 26 feminino) que apresentaram alteração na avaliação do processamento auditivo (central) associada à ausência do reflexo acústico. Resultados e Discussão os resultados demonstraram numericamente que as frequências com maior número de ausência do reflexo acústico, tanto na pesquisa contralateral quanto na ipsilateral, foram 4KHz, 3KHz e 500Hz respectivamente, para ambos os gêneros, mas, sem diferença significante no tratamento estatístico. Também, em ambos os grupos, as habilidades auditivas que apresentaram maior frequência de alterações foram figura fundo e ordenação temporal, que sobressaíram em número quando comparadas com as demais habilidades, e sem diferença significante no tratamento estatístico realizado com os testes de Fisher, Quiquadrado e Anova. Conclusão os resultados da presente pesquisa nos levam a concluir que as estruturas do sistema nervoso auditivo central responsáveis pelo sistema do arco reflexo do músculo estapédio, também relacionam-se aos mecanismos fisiológicos auditivos das habilidades auditivas, o que evidencia a possível relação entre a ausência do RA com alterações do distúrbio do processamento auditivo (central). .

Purpose to characterize and relate the findings of the acoustic reflex of the stapedial muscle in individuals diagnosed with Auditory Processing Disorder. Methods descriptive retrospective cross-sectional research submitted and approved by the Ethics in Research Committee, under protocol number 0047/11. The sample consisted of 83 individuals (57 males and 26 females), who showed abnormalities in auditory processing associated with the absence of acoustic reflex. Results and Discussion the results showed that the frequencies which lack more in the acoustic reflex both in the ipsilateral and in contralateral research were 4000 Hz, 3000 Hz and 500 Hz, respectively for both, but without significant difference in the statistical analysis. Also, in both groups the auditory skills which presented more change frequency were the speech in noise and temporal ordering which called the attention to their number when compared to other skills without significant difference in the statistical analysis performed by the Fisher, chi-square and ANOVA tests. Conclusion with shown results we can conclude that the nervous system structures for the central hearing are responsible for the bridge reflex system of the stapedial muscle, which also relate to the acoustic physiologic of the auditory skills which shows a possible relation to the lack of RA to the changes of the disorder of the (central) auditory processing .

Perfil das crianças atendidas no setor fonoaudiológico do ambulatório de crianças de alto risco da prefeitura municipal de Franca/SP / Profile of children attended in the speech therapy department of the high risk children clinic in Franca/SP

OBJETIVO: caracterizar o perfil das crianças atendidas no setor fonoaudiológico do ambulatório de crianças de alto risco da Prefeitura Municipal de Franca- SP. MÉTODO: trata-se de um estudo descritivo do tipo transversal e contemporâneo, realizado por meio da consulta de 62 prontuários de recém-nascidos atendidos no ano de 2010. RESULTADOS: os resultados revelaram que a maioria da amostra era composta por neonatos do gênero masculino; prematuros, com média de 32 semanas de idade gestacional; baixo peso ao nascer e crescimento intra-uterino adequado; peso médio de 1.774 gramas; fazendo uso de sondas para a alimentação, sendo a sonda parenteral a mais utilizada; ingestão de leite materno associado à fórmula; presença dos reflexos de busca, sucção, mordida e gap. O tempo médio que os bebês levaram para passar para a via oral exclusiva foi de três semanas. A frequência média de atendimentos fonoaudiológicos recebidos ficou em sete estimulações. Verificou-se que os aspectos que interferem na transição da via de alimentação do recém-nascido para via oral exclusiva são: prematuridade e a classificação do peso. CONCLUSÃO: os dados obtidos nessa pesquisa apontam a importância da intervenção fonoaudiológica com relação à estimulação precoce da sucção em recém-nascido pré-termo, estando relacionada com o desenvolvimento global do bebê. A estimulação precoce realizada pelos fonoaudiólogos nos recém-nascidos pré-termos é fundamental para uma alimentação adequada e nutritiva.

PURPOSE: to define the profile of children attended in the speech therapy department of the high risk children clinic in Franca/SP. METHOD: it is a cross-sectional descriptive study and contemporary, performed by consulting the records of 62 infants treated during 2010. RESULTS: the results showed that the majority of the sample consisted of male newborns, premature infants, with an average of 32 weeks gestational age, low birth weight and appropriate intrauterine growth, with average weight of 1,774 grams, using probes for food, and the most widely used is parenteral; associated with ingesting milk formula, with the presence of reflexes of searching, sucking, biting and gap. The average number of weeks that babies took to switch to oral feeding was three weeks. The average speech therapy sessions received was seven stimulations. It was found that the issues that interfere with the newborn transition to the oral feeding only are exclusively prematurity and weight classification. CONCLUSION: the data obtained in this study point to the effectiveness of speech therapy intervention in the early stimulation of sucking in newborn pre-term, in relation to the global baby development. Early stimulation of speech therapy in newborn preterm infants is critical for an adequate and nutritious feeding.

Verificação das respostas do Mismatch Negativity (MMN) em sujeitos idosos / Mismatch Negativity (MMN) response studies in elderly subjects

Mismatch Negativity é potencial endógeno que reflete o processamento de diferenças ocorridas no estímulo acústico. Objetivo: Caracterizar as respostas do MMN em sujeitos idosos, comparar com sujeitos adultos. Material e método: Estudo prospectivo, com 30 sujeitos, 15 do gênero masculino e 15 do gênero masculino, com idade entre 60 e 80 anos e 11 meses. Teste estatístico Mann-Whitney. Os sujeitos passaram por avaliação médica e pelos exames de Audiometria Tonal Liminar, Imitanciometria, Emissões Otoacústicas e Potenciais Auditivos de Curta e Longa Latência (MMN). Resultados: A latência média foi de 161,33ms (CZA2) e 148,67ms (CZA1), gênero feminino; de 171ms (CZA2) e 159,07ms (CZA1), gênero masculino. A amplitude média foi de -2,753µV (CZA2) e -2,177µV (CZA1), gênero feminino; de -1,847µV (CZA2) e -1,953µV (CZA1), gênero masculino. Quanto aos hemisférios direito e esquerdo, variável latência, média de 166ms (CZA2) e 153,87ms (CZA1); para a variável amplitude, média de -2,316µV (CZA2) e -2,065µV (CZA1). Conclusão: Não há diferença estatística significante entre as variáveis latência e amplitude, ao se comparar os gêneros masculino e feminino, os lados direito e esquerdo nos sujeitos idosos e entre as idades cronológicas adultos e idosos.

Mismatch Negativity is an endogenous potential which reflects the processing of differences incurred in the acoustic stimulus. AIM: to characterize MMN responses in elderly subjects and compare with adult subjects. Materials and methods: prospective study involving 30 subjects, 15 men and 15 women, aged between 60 and 80 years and 11 months. Statistical test: Mann-Whitney. The subjects went through medical evaluation, threshold tonal audiometry, immittance tests, otoacoustic emissions and short and long latency auditory potentials (MMN). Results: mean latency was 161.33 ms (CZA2) and 148.67 ms (CZA1), in women; of 171 ms (CZA2) and 159.07 ms (CZA1), men. Mean amplitude was -2.753 µV (CZA2) and -2.177 µV (CZA1), women; -1.847 µV (CZA2) and -1.953 µV (CZA1), men. As to the right and left hemispheres, mean latency variable of 166 ms (CZA2) and 153.87 ms (CZA1); for the amplitude variable, mean value of -2.316 µV (CZA2) and -2.065 µV (CZA1). Conclusion: there is no statistically significant difference between the latency and amplitude when we compared males and females, right and left sides in the elderly and between chronologic ages between adults and elderly subjects.